Pathway Tools
Intro Tutorial
discounted registration ends Sept 5, 2015
Pathway Tools
Intro Tutorial
discounted registration ends Sept 5, 2015
Pathway Tools
Intro Tutorial
discounted registration ends Sept 5, 2015
Pathway Tools
Intro Tutorial
discounted registration ends Sept 5, 2015
Pathway Tools
Intro Tutorial
discounted registration ends Sept 5, 2015

Escherichia coli K-12 substr. MG1655 Enzyme: proline aminopeptidase P II

Gene: pepP Accession Numbers: EG10697 (EcoCyc), b2908, ECK2903

Regulation Summary Diagram: ?

Regulation summary diagram for pepP

Subunit composition of proline aminopeptidase P II = [PepP]4

Aminopeptidase P is an exopeptidase that cleaves the amino-terminal residue from polypeptides, as long as the following residue is a proline [Yoshimoto88, Yoshimoto94].

Aminopeptidase P comprises four PepP monomers, arranged as a dimer of dimers [Yoshimoto88, Wilce98]. Kinetic and structural analysis of PepP has identified residues comprising the active site as well as parts of its structure that are required for substrate specificity [Graham06].

pepP is one of a network of 93 genes believed to play a role in promoting the stress-induced mutagenesis (SIM) response of E. coli K-12 [Al12].

Citations: [Yaron68, Fleminger82]

Locations: cytosol

Map Position: [3,051,537 <- 3,052,862] (65.77 centisomes, 237°)
Length: 1326 bp / 441 aa

Molecular Weight of Polypeptide: 49.815 kD (from nucleotide sequence)

Unification Links: ASAP:ABE-0009549 , CGSC:28682 , DIP:DIP-10459N , EchoBASE:EB0691 , EcoGene:EG10697 , EcoliWiki:b2908 , Mint:MINT-1252312 , ModBase:P15034 , OU-Microarray:b2908 , PortEco:pepP , PR:PRO_000023511 , Pride:P15034 , Protein Model Portal:P15034 , RefSeq:NP_417384 , RegulonDB:EG10697 , SMR:P15034 , String:511145.b2908 , UniProt:P15034

Relationship Links: InterPro:IN-FAMILY:IPR000994 , InterPro:IN-FAMILY:IPR001131 , InterPro:IN-FAMILY:IPR001714 , InterPro:IN-FAMILY:IPR007865 , InterPro:IN-FAMILY:IPR028980 , InterPro:IN-FAMILY:IPR029149 , PDB:Structure:1A16 , PDB:Structure:1JAW , PDB:Structure:1M35 , PDB:Structure:1N51 , PDB:Structure:1W2M , PDB:Structure:1W7V , PDB:Structure:1WBQ , PDB:Structure:1WL6 , PDB:Structure:1WL9 , PDB:Structure:1WLR , PDB:Structure:2BH3 , PDB:Structure:2BHA , PDB:Structure:2BHB , PDB:Structure:2BHC , PDB:Structure:2BHD , PDB:Structure:2BN7 , PDB:Structure:2BWS , PDB:Structure:2BWT , PDB:Structure:2BWU , PDB:Structure:2BWV , PDB:Structure:2BWW , PDB:Structure:2BWX , PDB:Structure:2BWY , PDB:Structure:2V3X , PDB:Structure:2V3Y , PDB:Structure:2V3Z , Pfam:IN-FAMILY:PF00557 , Pfam:IN-FAMILY:PF05195 , Prints:IN-FAMILY:PR00599 , Prosite:IN-FAMILY:PS00491 , Smart:IN-FAMILY:SM01011

In Paralogous Gene Group: 58 (3 members)

Gene-Reaction Schematic: ?

Gene-Reaction Schematic

GO Terms:

Biological Process: GO:0006508 - proteolysis Inferred by computational analysis [UniProtGOA11, GOA01a]
Molecular Function: GO:0004177 - aminopeptidase activity Inferred from experiment Inferred by computational analysis [UniProtGOA11, GOA01a, Yoshimoto88]
GO:0005515 - protein binding Inferred from experiment [Butland05]
GO:0008233 - peptidase activity Inferred by computational analysis [UniProtGOA11]
GO:0008235 - metalloexopeptidase activity Inferred by computational analysis [GOA01a]
GO:0008237 - metallopeptidase activity Inferred by computational analysis [UniProtGOA11]
GO:0016787 - hydrolase activity Inferred by computational analysis [UniProtGOA11]
GO:0030145 - manganese ion binding Inferred by computational analysis [GOA01a]
GO:0046872 - metal ion binding Inferred by computational analysis [UniProtGOA11]
Cellular Component: GO:0005829 - cytosol Inferred from experiment Inferred by computational analysis [DiazMejia09, Ishihama08, Lasserre06]
GO:0005737 - cytoplasm Inferred by computational analysis [UniProtGOA11a, UniProtGOA11]

MultiFun Terms: information transfer protein related turnover, degradation
metabolism degradation of macromolecules proteins/peptides/glycopeptides

Essentiality data for pepP knockouts: ?

Growth Medium Growth? T (°C) O2 pH Osm/L Growth Observations
LB enriched Yes 37 Aerobic 6.95   Yes [Gerdes03, Comment 1]
LB Lennox Yes 37 Aerobic 7   Yes [Baba06, Comment 2]
M9 medium with 1% glycerol Yes 37 Aerobic 7.2 0.35 Yes [Joyce06, Comment 3]
MOPS medium with 0.4% glucose Yes 37 Aerobic 7.2 0.22 Yes [Baba06, Comment 2]

Revised 25-May-2011 by Brito D

Enzymatic reaction of: proline aminopeptidase

EC Number:

a peptide + H2O <=> a standard α amino acid + a peptide

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the direction in which it was curated.

The reaction is physiologically favored in the direction shown.

Cofactors or Prosthetic Groups: Mn2+ [Wilce98]

Activators (Unknown Mechanism): Mn2+ [Yoshimoto89]

pH(opt): 7.8 [BRENDA14, Fleminger82], 8.5 [BRENDA14, Yoshimoto88]

Sequence Features

Protein sequence of PepP with features indicated

Feature Class Location Citations Comment
Cleavage-of-Initial-Methionine 1
[Yoshimoto89, UniProt11]
UniProt: Removed.
Chain 2 -> 441
UniProt: Xaa-Pro aminopeptidase;
Metal-Binding-Site 261
UniProt: Manganese 2.
Metal-Binding-Site 272
UniProt: Manganese 1.
Metal-Binding-Site 355
UniProt: Manganese 1.
Metal-Binding-Site 384
UniProt: Manganese 1.
Metal-Binding-Site 407
UniProt: Manganese 1.

Gene Local Context (not to scale): ?

Gene local context diagram

Transcription Unit:

Transcription-unit diagram


10/20/97 Gene b2908 from Blattner lab Genbank (v. M52) entry merged into EcoCyc gene EG10697; confirmed by SwissProt match.


Al12: Al Mamun AA, Lombardo MJ, Shee C, Lisewski AM, Gonzalez C, Lin D, Nehring RB, Saint-Ruf C, Gibson JL, Frisch RL, Lichtarge O, Hastings PJ, Rosenberg SM (2012). "Identity and function of a large gene network underlying mutagenic repair of DNA breaks." Science 338(6112);1344-8. PMID: 23224554

Baba06: Baba T, Ara T, Hasegawa M, Takai Y, Okumura Y, Baba M, Datsenko KA, Tomita M, Wanner BL, Mori H (2006). "Construction of Escherichia coli K-12 in-frame, single-gene knockout mutants: the Keio collection." Mol Syst Biol 2;2006.0008. PMID: 16738554

BRENDA14: BRENDA team (2014). "Imported from BRENDA version existing on Aug 2014."

Butland05: Butland G, Peregrin-Alvarez JM, Li J, Yang W, Yang X, Canadien V, Starostine A, Richards D, Beattie B, Krogan N, Davey M, Parkinson J, Greenblatt J, Emili A (2005). "Interaction network containing conserved and essential protein complexes in Escherichia coli." Nature 433(7025);531-7. PMID: 15690043

DiazMejia09: Diaz-Mejia JJ, Babu M, Emili A (2009). "Computational and experimental approaches to chart the Escherichia coli cell-envelope-associated proteome and interactome." FEMS Microbiol Rev 33(1);66-97. PMID: 19054114

Fleminger82: Fleminger G, Carmel A, Goldenberg D, Yaron A (1982). "Fluorogenic substrates for bacterial aminopeptidase P and its analogs detected in human serum and calf lung." Eur J Biochem 125(3);609-15. PMID: 6749499

Gerdes03: Gerdes SY, Scholle MD, Campbell JW, Balazsi G, Ravasz E, Daugherty MD, Somera AL, Kyrpides NC, Anderson I, Gelfand MS, Bhattacharya A, Kapatral V, D'Souza M, Baev MV, Grechkin Y, Mseeh F, Fonstein MY, Overbeek R, Barabasi AL, Oltvai ZN, Osterman AL (2003). "Experimental determination and system level analysis of essential genes in Escherichia coli MG1655." J Bacteriol 185(19);5673-84. PMID: 13129938

GOA01a: GOA, DDB, FB, MGI, ZFIN (2001). "Gene Ontology annotation through association of InterPro records with GO terms."

Graham06: Graham SC, Lilley PE, Lee M, Schaeffer PM, Kralicek AV, Dixon NE, Guss JM (2006). "Kinetic and crystallographic analysis of mutant Escherichia coli aminopeptidase P: insights into substrate recognition and the mechanism of catalysis." Biochemistry 45(3);964-75. PMID: 16411772

Ishihama08: Ishihama Y, Schmidt T, Rappsilber J, Mann M, Hartl FU, Kerner MJ, Frishman D (2008). "Protein abundance profiling of the Escherichia coli cytosol." BMC Genomics 9;102. PMID: 18304323

Joyce06: Joyce AR, Reed JL, White A, Edwards R, Osterman A, Baba T, Mori H, Lesely SA, Palsson BO, Agarwalla S (2006). "Experimental and computational assessment of conditionally essential genes in Escherichia coli." J Bacteriol 188(23);8259-71. PMID: 17012394

Lasserre06: Lasserre JP, Beyne E, Pyndiah S, Lapaillerie D, Claverol S, Bonneu M (2006). "A complexomic study of Escherichia coli using two-dimensional blue native/SDS polyacrylamide gel electrophoresis." Electrophoresis 27(16);3306-21. PMID: 16858726

Nakahigashi92: Nakahigashi K, Miyamoto K, Nishimura K, Inokuchi H (1992). "Isolation and characterization of a light-sensitive mutant of Escherichia coli K-12 with a mutation in a gene that is required for the biosynthesis of ubiquinone." J Bacteriol 1992;174(22);7352-9. PMID: 1339425

UniProt09: UniProt Consortium (2009). "UniProt version 15.8 released on 2009-10-01 00:00:00." Database.

UniProt11: UniProt Consortium (2011). "UniProt version 2011-06 released on 2011-06-30 00:00:00." Database.

UniProt15: UniProt Consortium (2015). "UniProt version 2015-01 released on 2015-01-16 00:00:00." Database.

UniProtGOA11: UniProt-GOA (2011). "Gene Ontology annotation based on manual assignment of UniProtKB keywords in UniProtKB/Swiss-Prot entries."

UniProtGOA11a: UniProt-GOA (2011). "Gene Ontology annotation based on the manual assignment of UniProtKB Subcellular Location terms in UniProtKB/Swiss-Prot entries."

Wilce98: Wilce MC, Bond CS, Dixon NE, Freeman HC, Guss JM, Lilley PE, Wilce JA (1998). "Structure and mechanism of a proline-specific aminopeptidase from Escherichia coli." Proc Natl Acad Sci U S A 95(7);3472-7. PMID: 9520390

Yaron68: Yaron A, Mlynar D (1968). "Aminopeptidase-P." Biochem Biophys Res Commun 32(4);658-63. PMID: 4878817

Yoshimoto88: Yoshimoto T, Murayama N, Honda T, Tone H, Tsuru D (1988). "Cloning and expression of aminopeptidase P gene from Escherichia coli HB101 and characterization of expressed enzyme." J Biochem (Tokyo) 104(1);93-7. PMID: 2851590

Yoshimoto89: Yoshimoto T, Tone H, Honda T, Osatomi K, Kobayashi R, Tsuru D (1989). "Sequencing and high expression of aminopeptidase P gene from Escherichia coli HB101." J Biochem (Tokyo) 105(3);412-6. PMID: 2659585

Yoshimoto94: Yoshimoto T, Orawski AT, Simmons WH (1994). "Substrate specificity of aminopeptidase P from Escherichia coli: comparison with membrane-bound forms from rat and bovine lung." Arch Biochem Biophys 311(1);28-34. PMID: 8185318

Report Errors or Provide Feedback
Please cite the following article in publications resulting from the use of EcoCyc: Nucleic Acids Research 41:D605-12 2013
Page generated by SRI International Pathway Tools version 19.0 on Mon Aug 31, 2015, biocyc13.